Benefits of near-universal vaccination and treatment access to manage COVID-19 burden in the United States

Background As we continue the fourth year of the COVID-19 epidemic, SARS-CoV-2 infections still cause high morbidity and mortality in the United States. During 2020–2022, COVID-19 was one of the leading causes of death in the United States and by far the leading cause among infectious diseases. Vaccination uptake remains low despite this being an effective burden reducing intervention. The development of COVID-19 therapeutics provides hope for mitigating severe clinical outcomes. This modeling study examines combined strategies of vaccination and treatment to reduce the burden of COVID-19 epidemics over the next decade. Methods We use a validated mathematical model to evaluate the reduction of incident cases, hospitalized cases, and deaths in the United States through 2033 under various levels of vaccination and treatment coverage. We assume that future seasonal transmission patterns for COVID-19 will be similar to those of influenza virus and account for the waning of infection-induced immunity and vaccine-induced immunity in a future with stable COVID-19 dynamics. Due to uncertainty in the duration of immunity following vaccination or infection, we consider three exponentially distributed waning rates, with means of 365 days (1 year), 548 days (1.5 years), and 730 days (2 years). We also consider treatment failure, including rebound frequency, as a possible treatment outcome. Results As expected, universal vaccination is projected to eliminate transmission and mortality. Under current treatment coverage (13.7%) and vaccination coverage (49%), averages of 81,000–164,600 annual reported deaths, depending on duration of immunity, are expected by the end of this decade. Annual mortality in the United States can be reduced below 50,000 per year with 52–80% annual vaccination coverage and below 10,000 annual deaths with 59–83% annual vaccination coverage, depending on duration of immunity. Universal treatment reduces hospitalizations by 88.6% and deaths by 93.1% under current vaccination coverage. A reduction in vaccination coverage requires a comparatively larger increase in treatment coverage in order for hospitalization and mortality levels to remain unchanged. Conclusions Adopting universal vaccination and universal treatment goals in the United States will likely lead to a COVID-19 mortality burden below 50,000 deaths per year, a burden comparable to that of influenza virus. Supplementary Information The online version contains supplementary material available at 10.1186/s12916-023-03025-z.

2. Optimistic: this estimate assumes that the only duplicate doses were those individuals completing their two-course series (i.e., dopt = dadmindseries).This yields an optimistic coverage estimate of 49%.
Future trends of COVID-19 vaccination uptake are assumed to follow influenza vaccination.The average proportion of vaccines administered in each month was calculated, then linearly interpolated to generate weekly estimates of vaccination rates.Because the age groups (6 months -4 years-old; 5-12 years-old, 13-17 years-old, 18-49 years-old, 50-64 years-old, and 65 years-old and above) in the data are different from the model, the age-specific number of new vaccinees were calculated from the coverage rate and the US census in 2020, and were allocated to the age groups in our model under an assumption of uniformity within each of the above age brackets.The weekly relative coverage rate was calculated by dividing the coverage rate this week by the total coverage achieved in the year.The age-specific annual relative coverage rate is used as the future trend of COVID-19 vaccination coverage.50% reduction in hospitalization compared to a population mixed with unvaccinated (15%) and vaccinated (85%) individuals (retrospective study)    S3.Doses administered between December 1, 2021, and November 30, 2022 (marked with vertical dashed lines) were used to estimate vaccine coverage in the 2022-2023 season.
parameters.† : Fitted parameters from previous studies.
Figure S1.Model diagram.Adapted from a previously published model[17-19] to show movement across compartments.Circled numbers on the upper-right corners refer to the number of repeated compartments (such as having six consecutive Exposed compartments).The grey arrows pointing out of compartments indicate COVID-associated deaths.Changes made include adding a one-stage vaccine compartment (Vac), waning of infection-induced and vaccineinduced immunity, and fast recovery from infection given treatment.The green solid line indicates the vaccine-seeking behavior, where only susceptible and recovered individuals will benefit from vaccination.The green dashed line indicates the waning immunity acquired from infection or vaccination.The red solid line indicates the fast recovery of the infected individuals after successful treatment.Infected individuals with failed treatment continue a normal progress of infection.

Figure S2 .
FigureS2.Calibrated output (red points) compared to observed data (black line) in RI (left) and the US (right).After June 6, 2021 (grey vertical dashed line), population mixing rates were calibrated to the hospitalized data in RI.New cases and new deaths in RI were simulated based on calibrated population mixing rates.The new cases, hospitalizations, and deaths in the US were scaled up from RI using the ratio of the total cases in different variant-dominant period between RI and the US.The scaled-up outputs for the US match the trends in the observed data.

Figure S3 .
Figure S3.Cumulative doses of COVID-19 vaccines administered in the United States.See detailed description in S1 Text and TableS3.Doses administered between December 1, 2021, and November 30, 2022 (marked with vertical dashed lines) were used to estimate vaccine coverage in the 2022-2023 season.
Figure S4.Coverage of Paxlovid in 50 states as of Dec 11, 2022.This is calculated as the cumulative administered courses of Paxlovid on Dec 11, 2022, divided by the number of patients from Jan 1, 2022, to Dec 11, 2022.

Figure S5 .
Figure S5.Vaccination coverage in 50 states between Dec 1, 2021, and Nov 30, 2022.Coverage is calculated as the number of administered doses of either a two-course primary series or booster divided by state-wide population (age > 6 months).

Figure S6 .
Figure S6.Weekly percentages of achieved coverage of influenza vaccination by age groups by calendar month.The trends observed were applied to COVID-19 vaccination administration in model projections.

Figure
Figure S7.Burden reduction slopes following treatment coverage under different vaccination coverages.Reductions in hospitalizations and deaths are more pronounced under lowvaccination circumstances.

Figure S8 .
Figure S8.Heatmaps of annual mortality under combinations of vaccine and treatment coverage under each transmission scenario and rate of immune waning.

Figure S9 .
Figure S9.Heatmaps of annual hospitalizations under of vaccine and treatment coverage under each transmission scenario and rate of immune waning.

Figure S10 .
Figure S10.Heatmaps of annual incident cases under combinations of vaccine and treatment coverage under each transmission scenario and rate of immune waning.

Figure S11 .Figure S12 .
Figure S11.Combinations of treatment coverage (horizontal axis) and vaccine coverage (vertical axis) that lead to COVID-19 mortality within the range of annual influenza mortality (10,000 -50,000 deaths) as well as below or over this range.The starred point in the plots represents the current treatment and vaccine coverage in the United States.

Figure S13 .
Figure S13.Annual burden between 2025 and 2033 given 20% probability of treatment failure.Vaccination coverage during the entire period is 49%.

Figure S14 .
Figure S14.Annual burden between 2025 and 2033 given 30% and 50% risk reduction to hospitalization after failed treatment.The assumed probability of unsuccessful treatment is 0.059.Vaccination coverage during the entire period is 49%.

Table S1 .
Estimated durations of immunity following vaccination or infection from literature.

Table S2 :
Updated clinical parameters for the Omicron variant.Clinical parameters retained from prior time periods have been previously fitted and published[17, 18].Citations within cells apply to all parameter values within the cell.